Eco-evolutionary dynamics on deformable fitness landscapes

Conventional approaches to modelling ecological dynamics often do not include evolutionary changes in the genetic makeup of component species and, conversely, conventional approaches to modelling evolutionary changes in the genetic makeup of a population often do not include ecological dynamics. But recently there has been considerable interest in understanding the interaction of evolutionary and ecological dynamics as coupled processes. However, in the context of complex multi-species ecosytems, especially where ecological and evolutionary timescales are similar, it is difficult to identify general organising principles that help us understand the structure and behaviour of complex ecosystems. Here we introduce a simple abstraction of coevolutionary interactions in a multi-species ecosystem. We model non-trophic ecological interactions based on a continuous but low-dimensional trait/niche space, where the location of each species in trait space affects the overlap of its resource utilisation with that of other species. The local depletion of available resources creates, in effect, a deformable fitness landscape that governs how the evolution of one species affects the selective pressures on other species. This enables us to study the coevolution of ecological interactions in an intuitive and easily visualisable manner. We observe that this model can exhibit either of the two behavioural modes discussed in the literature; namely, evolutionary stasis or Red Queen dynamics, i.e., continued evolutionary change. We find that which of these modes is observed depends on the lag or latency between the movement of a species in trait space and its effect on available resources. Specifically, if ecological change is nearly instantaneous compared to evolutionary change, stasis results; but conversely, if evolutionary timescales are closer to ecological timescales, such that resource depletion is not instantaneous on evolutionary timescales, then Red Queen dynamics result. We also observe that in the stasis mode, the overall utilisation of resources by the ecosystem is relatively efficient, with diverse species utilising different niches, whereas in the Red Queen mode the organisation of the ecosystem is such that species tend to clump together competing for overlapping resources. These models thereby suggest some basic conditions that influence the organisation of inter-species interactions and the balance of individual and collective adaptation in ecosystems, and likewise they also suggest factors that might be useful in engineering artificial coevolution

Expression of BDNF and trkB as a function of age and cognitive performance

The expression of the neurotrophic factor BDNF increases during learning-related events and is decreased in the hippocampus of Alzheimer's Disease patients, suggesting that it plays a role in learning, memory, and/or age-related memory deficits. We examined the expression of BDNF and its high affinity receptor, trkB, in young and aged Sprague-Dawley rats. BDNF and trkB mRNA were measured by semi-quantitative in situ hybridization and BDNF protein was measured by ELISA. Significant decreases with age were detected for BDNF mRNA in the pons, BDNF protein in the midbrain, and trkB mRNA in many areas of the brain. Rats were evaluated on the Morris water maze before sacrifice so that BDNF and trkB levels could be related to cognitive status. Regression analyses revealed that decreased trkB mRNA in the pons significantly predicted impaired memory performance in aged rats. These results suggest that decreases in trkB mRNA with age are more widespread than decreases in BDNF, and that BDNF decreases are restricted to more caudal brain regions

In situ hybridization of trkB and trkC receptor mRNA in rat forebrain and association with high-affinity binding of [125I]BDNF, [125I]NT-4/5 and [125I]NT-3

The TrkB and TrkC receptor tyrosine kinases have been identified as high-affinity receptors for the neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and NT-3 respectively. These receptor classes were identified and mapped by the in situ hybridization of antisense riboprobes complementary to portions of the intracellular (tyrosine kinase) or extracellular (ligand-binding) domains of trkB and trkC mRNA, and by the distribution of high-affinity [125I]BDNF, [125I]NT-4/5 and [125I]NT-3 binding sites in adjacent rat brain sections. Both methods showed that TrkB and TrkC receptors are abundant and widely expressed throughout the brain. Kinase or extracellular domain trkC probes labelled neuronal somata in a qualitatively similar manner in virtually every major area of the forebrain. Neither trkC probe labelled non-neuronal cells except for elements within cerebral arteries and arterioles. The kinase domain trkB probe hybridized exclusively to neurons. Neurons expressing trkB were even more widely distributed than those expressing trkC. The extracellular domain trkB probe labelled neurons with the same relative distribution as the trkB kinase domain probe, but also hybridized extensively with non-neural cells, particularly astrocytes, ependyma and choroid epithelium cells. The distribution of [125I]NT-3 binding sites generally resembled that of trkC hybridization, particularly in the neocortex, striatum and thalamus. [125I]BDNF and [125I]NT-4/5 binding sites were more widely distributed and denser than those for [125I]NT-3, and resembled the trkB hybridization pattern. These patterns are consistent with the preferential binding in the brain of TrkC receptors by [125I]NT-3 and of TrkB receptors by [125I]BDNF and [125I]NT-4/5. That the predominantly neuronal patterns of hybridization obtained with kinase and extracellular domain probes for trkC are qualitatively indistinguishable suggests that truncated and full-length forms of TrkC are expressed within extensively overlapping populations of neurons. In marked contrast to TrkC, expression of the full-length and truncated forms of TrkB appears to be largely segregated, being expressed principally on neurons and non-neuronal cells respectively. The abundant and widespread neuronal distribution of full-length, signal-transducing forms of TrkB and TrkC predict that their cognate ligands, BDNF, NT-4/5 and NT-3, may exert direct effects on a large proportion of neurons within the mature brain

Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes

Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75(LNGFR). In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFRα) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte

Soluble immune markers in the different phases of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection